B-cell chronic lymphocytic leukemias (10 of 10), follicular lymphomas (9 of 9), mucosa-associated lymphoid tissue lymphomas (5 of 5) and reactive lymphoid tissues with the exception of normal spleen had no or very low cyclin D1 expression.
In parallel, we investigated the relationship between p27(Kip1), the lymphoma proliferation index, Epstein-Barr virus status, expression of cellular cyclin D3 and cyclin D1, and B-cell differentiation stage.
Statistical analysis of the expression data revealed the combination of CCND1 and CDK4 as the best classifier concerning separation of both lymphoma types.
Rearrangements of the bcl-1, 2, 6, and c-myc gene correlated with the clinical outcome in DLBL and may thus serve as prognostic markers in patients with this form of malignant lymphoma.
The latter parameters and IPI were the only ones with independent prognostic value (RR = 10, 5.0, 6.7, and 3.7, respectively; P < 0.001) when assessed together with lymphoma sub-type, primary versus relapse cases, treatment, B symptoms, S phase fraction, and presence of BCL1 and BCL2 translocations.
We examined 151 cases of lymphoma with MCL morphology from a viewpoint of cyclin D1 overexpression, which is now easily detectable by immunohistochemistry.
In the present study, we analysed 34 de novo diffuse large B cell lymphoma (DLCL) from a population-based lymphoma registry for alterations of the RB1 pathway at the genetic (RB1 and CDK4) and protein (pRb, cyclin D1, cyclin D3, CDK4, and E2F-1) level.
The contribution of other chromosomal abnormalities other than bcl-1 and bcl-2 rearrangements in the pathogenesis of MCL and follicular-cell lymphomas has to be determined.
Lymphoma cell lines harboring the t(11;14) showed cyclin D1 protein but no or very low levels of cyclin D3; three other B-cell lines, a T-cell line, and peripheral blood lymphocytes strongly expressed cyclin D3 and reacted negatively for cyclin D1.
These results indicated that positive nuclear staining of lymphoma cells by 5D4 antibody reflects PRAD1/cyclin D1 mRNA expression, and showed that this monoclonal antibody has diagnostic value for differentiating MCL from other types of lymphomas.
CYCLIN D1, a cell-cycle control gene, recently has been shown to be identical to an oncogene alternatively known as BCL-1 and PRAD1 and implicated in centrocytic lymphomas and parathyroid adenomas, respectively.
Cyclin D1, an oncogene that has a critical role in G1 progression of the cell cycle, has been observed to be amplified in carcinomas of the breast and head and neck, and translocated in parathyroid adenomas and centrocytic lymphomas.
In particular, the recognition of chromosomal translocations which have activated the BCL1 and BCL2 proto-oncogenes have strong associations with specific types of non-Hodgkin's malignant lymphomas such as mantle cell lymphoma and follicular center cell lymphoma, respectively.
The coincidence of anaplastic and sometimes blast-like morphology of the tumour cells, high proliferation index and a rearranged bcl-1 gene in nearly all cases of anaplastic centrocytic lymphoma support their classification as high-grade malignant variants of centrocytic lymphoma and suggest a possible role for the bcl-1 locus not only in the origin but also in the progression of centrocytic lymphomas.
Immunohistochemical expression of PRAD1/cyclin D1 protein has been investigated in 106 tissue specimens of 104 cases of lymphoma, non-neoplastic lymphoid disorders and other hematologic malignancies by employing the monoclonal antibody 5D4 with formalin-fixed paraffin-embedded sections, using the microwave oven heating method.
The PRAD1 gene, located at 11q13, has been implicated in the pathogenesis of a variety of tumors, including parathyroid adenomas, t(11;14) bearing B-lymphoid tumors (particularly centrocytic lymphomas) where it is highly likely to be the BCL1 oncogene, and possibly in breast carcinomas and squamous cell cancers of the head and neck as well.